The aim of this study was to detect the association of the cytochrome P450 (CYP) 17 T-34C and CYP19 T<C polymorphisms with the risk of acne vulgaris (AV). The study enrolled 198 patients with AV (mild, moderate and severe) and 195 unrelated age-matched healthy controls from western Iran who had Kurdish ethnic background. The presence of the CYP17 TC genotype significantly increased the risk of mild, moderate and severe AV by 2.68, 2.28 and 2.94 times, respectively, while the presence of the CYP19 TC genotype significantly elevated the risk of overall AV and mild AV by 2.1 and 3.2 times, respectively. There was a synergy between the CYP 17 TC and CYP19 TT genotypes, which increased the risk of AV by 2.45-fold (P < 0.001). To our knowledge, this is the first study showing that the CYP17 T-34C and CYP19 T<C variants and their synergy are associated with susceptibility to AV in an Iranian population.